MHC class II antigens, HLA-DR in the human and Ia in the mouse, are membrane bound glycoproteins that are encoded by genes of the major histocompatibility complex. Expression of these antigens is of great functional importance for the initiation and perpetuation of immune responses. In a number of immunopathologic conditions HLA- DR antigen negative cells are stimulated to express class II antigens. In these cases an immunologic role has been postulated for the class II antigen expression. During the past year, we have determined if class II antigens are expressed in certain diseases as well as evaluated their possible role in autoimmune and inflammatory diseases. Initial studies identified cells in the anterior segment and cells in the retina (rpe cell) which express class II antigens during inflammatory eye diseases. Treatment with monoclonal anti-Ia antibodies diminished the clinical disease and the expression of MHC class II antigens. These studies on MHC class II antigen expression in localized autoimmune diseases provide evidence that the activation of these antigens may contribute to the immunopathogenesis of these diseases.